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ABSTRACT: This experiment was designed to determine whether hydrogen (H(2)) rich saline can ameliorate brain abnormalities in a rat model with acute carbon monoxide (CO) poisoning.
Sprague-Dawley male rats were used for CO poisoning and H(2) rich saline treatment. Changes in neurons, microglias, and myelin sheath were observed by electron microscope. Neuron loss was assessed by Nissl staining. Antioxidant capacities were evaluated by studying superoxide dismutase activities and malondialdehyde concentration in the brain and serum. Infiltration of macrophages, expression of immune-associated cytokines (MIP-1-alpha and ICAM-1), and changes in myelin basic protein (MBP) were monitored by immunohistochemical staining and western blotting.
CO-exposed rats showed the increase in neuron loss and the decrease in antioxidant capacities. And H(2) rich saline given after CO poisoning can prevent the alterations mentioned above. CO-mediated oxidative stress caused alterations in MBP, which initiated an adaptive immunological response that led to brain injury. MBP from H(2) rich saline-treated, CO-exposed rats was recognized normally by immunohistochemical staining and western blotting. Electron microscope observation from CO-exposed rats showed an apparent aggregation of microglias. Macrophages from CO-exposed rats were significantly more than those from H(2) rich saline-treated and control rats, and the immunofluorescence observation showed that macrophages were similar to microglias in type. Expression levels of MIP-1-alpha and ICAM-1 increased in the brains of CO-poisoned rats and H(2) rich saline treatment decreased the levels.
The results indicate that H(2) rich saline prevents immune-mediated brain injury after CO poisoning.
Neurological Research 12/2012; 34(10):1007-15. · 1.52 Impact Factor
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ABSTRACT: BACKGROUND: Studies have shown that inhalation of hydrogen gas, which acts as an antioxidant, can protect the brain against free radicals in rats with ischemia-reperfusion. The neuronal damage caused by acute carbon monoxide (CO) poisoning is partly free radical mediated. We hypothesize that hydrogen may prevent neurological damage from CO poisoning. OBJECTIVES: This study is designed to test whether hydrogen (H(2))-rich saline will have a protective effect on rats with acute CO poisoning. METHODS: Male Sprague-Dawley rats were subjected to CO poisoning. H(2)-rich saline was administered by peritoneal injection (6mL/kg/24h). We used the Morris water maze and the open field test to determine cognitive function. After cognitive function studies, rats were decapitated and the levels of trace elements copper (Cu), zinc (Zn), and iron (Fe) in serum and brain were assessed by flame atomic absorption spectrometry. Necrosis, apoptosis, and autophagy of neurons were assessed by H-E staining and immunohistochemical staining in another group of rats. RESULTS: H(2)-rich saline treatment improved the cognitive deficits and reduced the degree of necrosis, apoptosis, and cell autophagy in rats. Additionally, H(2)-rich saline decreased the content of Fe in serum and brain in these rats, and increased the content of serum Cu related to free radical metabolism. CONCLUSIONS: H(2)-rich saline may effectively protect the brain from injury after acute CO poisoning. The mechanism of this protection may be related to lessening oxidative damage by affecting trace elements in vivo.
Journal of Emergency Medicine 08/2012; · 1.31 Impact Factor
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ABSTRACT: Cacna1f gene mutation could lead to incomplete congenital stationary night blindness (iCSNB) disease. The CSNB-like phenotype rat is a spontaneous rat model caused by Cacna1f gene mutation. The present study explored the phenotypic properties of behavior performance in CSNB rats further. The vision-related behaviors of CSNB rats were assessed with a Morris water maze (MWM), passive avoidance tests, and open-field test. Motor ability was evaluated with a rotarod test and a wire hang test, and mechanical pain and thermalgia were used to evaluate sensory system function. Electroretinograms (ERGs) were recorded to evaluate the function of the retina. The vision-related results showed that longer latencies of escape and reduced probe trial in MWM for CSNB rats. There were more errors in avoidance test; CSNB rats were more active in the open field and presented a different pattern of exploration. The locomotor-related behaviors showed shorter falling latencies in the rotarod test and shorter gripping time in CSNB rats. And mechanical thresholds of pain increased in CSNB rats. The ERGs indicated that both the amplitude and latency of rod and cone systems were impaired in the CSNB rats. In summary, Cacna1f gene mutation changed the performance of various behaviors in the CSNB rat aside from vision-related phenotype. Cacna1f gene might play a role in a wide range of responses in the organism. These results confirm the importance of a comprehensive profile for understanding the behavior phenotype of Cacna1f gene mutation in CSNB rat.
Journal of neurogenetics 07/2012; · 0.73 Impact Factor
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ABSTRACT: This work was conducted to determine whether congenital stationary night blindness (CSNB), which is caused by a Cacna1f mutation, could affect development of second-order neurons in the retina, such as horizontal cells (HCs). The CSNB rats and age-matched wild type rats were sacrificed at postnatal days (PND) 15, 30 and 60. Morphometric analyses of HCs, which were labeled by a primary antibody to calbindin D-28K, were performed at the light microscopic level on retinal cross sections and whole mount retinas. Calbindin D-28K was measured by western blotting in retinal samples. We found that the average number and density of HCs, Calbindin level and thickness of OPL were all decreased significantly in CSNB group compared to control group. These results indicated that second-order retinal neurons, such as horizontal cells, are affected by retinal degeneration. The relationship between the absence of HCs and the gene defect of CSNB requires further research.
Neuroscience Letters 05/2012; 521(1):26-30. · 2.11 Impact Factor
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ABSTRACT: The disease-causing gene which underlies a naturally occurring X-linked mutant cone dysfunction Sprague-Dawley rat model was investigated. Full-field electroretinogram (ERG) and simple sequence length polymorphism analyses were applied to 441-second filial generation rats that were derived from crossing a mutant rat and a Brown-Norway rat. After identifying a mutation mapping within the telomeric region of chromosome X, a candidate gene related to retinal cone function in this region was further screened using real-time PCR, immunohistochemistry and histological methods. The results showed that a G-to-T substitution at the splice acceptor site of intron 4 was present in the opsin 1, medium-wave sensitive (Opn1mw) gene, thereby causing down-regulated transcription and translation. These changes were consistent with abnormities seen in the ERG response. However, there was no significant histological change in the mutant rat retina. Therefore, we infer from this that the causative gene for the mutation is Opn1mw and consequently term this a middle-wavelength opsin cone dysfunction (MCD) rat model. The deficiency in vision of the MCD rat is similar to the color vision defects that occur in humans with a color vision defect but without recessive retinal degeneration. This rat model may be useful for understanding the mechanism that is responsible for color vision and for developing clinical therapies for several retinal dystrophies caused by cone opsin deficiencies.
Experimental Eye Research 04/2010; 91(1):26-33. · 3.26 Impact Factor
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ABSTRACT: Myopic eyes show structural differences from normal eyes and may respond differently to microgravity, increasing the risk for possible development of ocular hypertension and glaucoma on orbit. In this experiment we used head-down rest (HDR) at an angle of 15 degrees to produce hydrostatic changes similar to acute exposure to microgravity.
There were 65 subjects (129 eyes) who were divided into groups characterized by refraction: emmetropes (N = 46; refraction error between -0.99 D and +0.10 D), low myopes (N = 39; > or = -1.0 D to < -3.0 D), and moderate myopes (N = 44; > or = -3.0 D to < -6.0 D). Each subject was studied resting in a horizontal position and after 1, 6, 11, 16, and 21 min of HDR. Measured variables included systolic and diastolic blood pressure (SBP and DBP, respectively), intraocular pressure (IOP), and ocular perfusion pressure (OPP).
The mean values of IOP increased significantly in all eyes during HDR, with IOP peaking at 6 min. Compared to emmetropes and low myopes, moderate myopes showed a significantly greater increase in IOP and higher peak values for IOP (18.6, 18.7, and 19.8 mmHg for emmetropes, low, and moderate myopes, respectively). Mean values of OPP in moderate myopes were significantly lower than in emmetropes and low myopes during HDR. Compared with baseline, mean SBP and DBP decreased obviously in emmetropes during HDR, while changes were minimal in the other groups.
Abnormal auto-regulation of ocular blood pressure in myopes of moderate and greater severity may pose a risk factor for developing ocular hypertension and possibly glaucoma when exposed to microgravity. HDR may offer a method of screening candidates for spaceflight for this risk prior to microgravity exposure.
Aviation Space and Environmental Medicine 04/2010; 81(4):418-22. · 0.88 Impact Factor
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Yonghao Gu,
Lifeng Wang,
Jie Zhou,
Qun Guo,
Na Liu,
Zhenqiang Ding,
Li Li,
Xinping Liu,
Jing An,
Guolin Yan,
Libo Yao, Zuoming Zhang
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ABSTRACT: To identify the gene mutation responsible for a previously described rat model of X-linked congenital stationary night blindness (CSNB).
Rat orthologous genes for Nyx and Cacna1f were isolated from retina through rapid amplification the cDNA ends (RACE) and examined for mutations. Electroretinograms were used to identify affected animals.
The rat Nyx cDNA spans 1,971 nucleotides and encodes a protein of 476 amino acids (GenBank: DQ393414). The rat Cacna1f cDNA spans 6,076 nucleotides and encodes a protein of 1,980 amino acids (GenBank: DQ393415). A c.2941C>T (p.R981Stop) mutation in Cacna1f was found in affected rats. Immunochemistry study showed labeling for rod bipolar and horizontal cells were reduced in affect retinas. For affected rats, b-wave and oscillatory potentials of scotopic ERG were absent, and b-wave of photopic ERG was clear but obviously reduced.
The Cacna1f mutation identified in the rat model of CSNB was predicted to lead to a protein product that is shortened by 999 amino acids, indicating that this is a model for the incomplete subtype of human X-linked CSNB (CSNB2). This rat model will be useful for defining the pathophysiological properties of this human disorder.
Molecular vision 01/2008; 14:20-8. · 2.20 Impact Factor
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ABSTRACT: To describe a possible spontaneous rat model of X-linked congenital stationary night blindness (CSNB).
Experimental animals were generated by mating the affected animal to normal rats, and from interbreeding littermates. To define the inheritance pattern, full-field electroretinograms (ERGs) were recorded from all progeny.
During the course of other experiments, an affected male rat was identified by a reduced amplitude ERG b-wave. When this rat was mated to normal Sprague-Dawley rats, all of the F1 progeny had normal ERG waveforms. When F1 offspring were interbred, 51% of the male offspring had b-wave reductions while all female offspring had normal ERG waveforms. When F1 females were backcrossed to the original affected male, b-wave reductions were noted in both male and female offspring; overall, 46.8% of the backcross progeny exhibited a b-wave reduction. In affected animals, the b-wave was selectively affected as the a-wave appeared to retain normal amplitude and kinetics at 1-4 months old. Cone ERGs were significantly reduced in amplitude and somewhat delayed. Similar ERG results were also obtained under the same stimulus conditions from human patients with complete CSNB (CSNB1).
The inheritance pattern is consistent with an X-linked recessive trait. The electrophysiological results suggest that this mutant rat line may provide another model for CSNB1.
Documenta Ophthalmologica 08/2003; 107(1):53-7. · 2.11 Impact Factor
